Suboptimal Prospects for Severe Malaria Treatment in the United States

Elongated Plasmodium falciparum gametocytes
Elongated Plasmodium falciparum gametocytes
Eli Lilly was the only pharmaceutical company providing quinidine gluconate in the United States, but in November 2017 it stopped manufacturing the drug and the remaining supplies expired.

Eli Lilly was the only pharmaceutical company providing quinidine gluconate in the United States, but in November 2017 it stopped manufacturing the drug and the remaining supplies expired. Clinicians’ ability to provide timely and effective treatment of severe malaria has been significantly hampered, according to an opinion article published in Annals of Internal Medicine.

To demonstrate the importance of the current options in the treatment of severe malaria in the US, the article authors used the hypothetical example of a young man recently returned from Cameroon, who exhibited fever and an altered mental state on presentation to an emergency department. A blood smear test for this patient shows 7% of erythrocytes infected with Plasmodium falciparum. The article authors highlighted that in severe presentations of malaria such as this, mortality risk is over 50%, and treatment within the first 24 hours, when mortality is highest, is imperative.

Two possible outcome scenarios for case like this are presented. In the first scenario, the only US Food and Drug Administration (FDA)-approved treatment for severe malaria in the country, intravenous quinidine, is readily available, and the patient is alert, oriented and symptomology is improved by the next day. In the second scenario, the closest available quinidine gluconate is 8 hours away by plane. This latter situation is one that is reality for many clinicians in the US since April 2019, when the remaining supplies of quinidine expired.

Intravenous medication is ideal for malaria treatment because it is the most effective way to reduce parasitemia, especially in cases of severe malaria where oral medications may not be well-tolerated. In endemic regions, injectable artesunate is the first-line treatment, but this drug is not FDA-approved, nor are there pending applications for its manufacture. In response to the unavailability of quinidine, the US Centers for Disease Control and Prevention (CDC) has announced that they will allow for injectable artesunate to be supplied by the US Army Medical Research and Materiel Command and available for all cases of severe malaria.

Although this treatment is effective, this counteracted by the difficulty in obtaining it. Clinicians must first call the CDC, and officials will then fly the artesunate from 1 of 10 depots throughout the US and deliver it to the nearest airport, after which the hospital is responsible for retrieval. The average time for delivery is reported to be 8 hours, but can take up to 24 hours, depending on the location of the patient. The CDC advises that oral antimalarial medications be started in place, if available, in this interim. However, oral medications are untenable in several clinical scenarios (eg, cerebral malaria, and hyperemesis), and further, are not as effective as IV medications.

The article authors stressed the need for solutions to this substandard level of care. They suggested that the CDC identify and pharmaceutical companies suitable for manufacturing intravenous artesunate and evaluate the need for providing incentives, including priority review of new drug applications, which could result in FDA approval in just 6 months. They also suggested that professional societies such as the American Society of Tropical Medicine and Hygiene and the Infectious Diseases Society of America advocate for malaria patients, and represent them in mediations with federal agencies, as well as in a petition for Eli Lilly to resume the manufacture of quinidine gluconate until supplies of artesunate are made available.

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Until a resolution is found, hospitals should develop preparedness plans to address differing scenarios, akin to the Ebola outbreak in 2014, and the US Department of Health and Human Services should offer guidance and coordinate a unified malaria preparedness plan. Rapid diagnostic tests and thick and thin blood smears should be swiftly administered to febrile patients who endorse a recent travel history to regions where malaria is endemic, and if the rapid diagnostic test indicates malaria, the CDC Malaria Hotline should be immediately contacted at (770)-488-7788, or (770)-488-7100 after hours. The process of obtaining intravenous artesunate should not be delayed while blood smears are being prepared. Plans for administering oral medications and transporting intravenous artesunate from the nearest airport should be in place, as well as plans for patient transfers, in cases where the hospital laboratory is not capable of providing the appropriate diagnostic tests.

The article authors concluded, “At present, the prospects for timely, effective treatment of severe malaria in the United States are grim. Careful preparation and action on the part of clinicians, hospitals, federal agencies, and professional societies are needed to prevent a catastrophe.”


Krey RA, Travassos MA. Severe malaria treatment in the United States at the precipice (published online August 20, 2019). Ann Intern Med. doi:10.7326/M19-1144